Crossover in a randomized trial can skew the interpretation of the efficacy of a cancer drug. In this Comment, I use examples from clinical trials presented at the 2023 ASCO annual meeting to highlight why ‘allowing’ crossover in randomized trials testing cancer drugs is problematic, and propose that crossovers should either be mandated or prohibited depending on the context.
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References
Im, S. A. et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N. Engl. J. Med. 381, 307–316 (2019).
Goetz, M. P. et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J. Clin. Oncol. 35, 3638–3646 (2017).
Sonke, G. S. et al. Primary outcome analysis of the phase 3 SONIA trial (BOOG 2017-03) on selecting the optimal position of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). J. Clin. Oncol. 41 (Suppl. 17), LBA1000–LBA1000 (2023).
Slamon, D. et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer: primary results from the phase III NATALEE trial. J. Clin. Oncol. 41 (Suppl. 17), LBA500–LBA500 (2023).
Tsuboi, M. et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2304594 (2023).
Kudo, M. et al. Efficacy, safety and patient reported outcomes (PROs) from the phase III IMbrave050 trial of adjuvant atezolizumab (atezo) + bevacizumab (bev) vs active surveillance in patients with hepatocellular carcinoma (HCC) at high risk of disease recurrence following resection or ablation. J. Clin. Oncol. 41 (Suppl. 16), 4002–4002 (2023).
Finn, R. S. et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med. 382, 1894–1905 (2020).
Mellinghoff, I. K. et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2304194 (2023).
Buckner, J. C. et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N. Engl. J. Med. 374, 1344–1355 (2016).
Gyawali, B. et al. Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring. ESMO Open 6, 100117 (2021).
Acknowledgements
B.G. receives salary support from Ontario Institute for Cancer Research funded by the Government of Ontario. The opinions expressed herein represent the author’s own opinions, and not those of the Government of Ontario.
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B.G. has acted as a consultant of Vivio Health.
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Gyawali, B. Problematic crossovers in cancer drug trials. Nat Rev Clin Oncol 20, 815–816 (2023). https://doi.org/10.1038/s41571-023-00805-7
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DOI: https://doi.org/10.1038/s41571-023-00805-7
